In mammals, variations in the rates of filtration of fluid at the glomerulus and in reabsorption of this filtrate by the renal tubules constitute the major defense of extracellular fluid volume against potentially disruptive effects of variations in intake and extrarenal loss of key solutes and water. This research program is aimed at clarifying our understanding of solute and water transport mechanisms operating at the level of individual renal tubules and capillaries that underlie these homeostatic adjustments. Clearance and micropuncture-microperfusion techniqes will be used to examine experimentally induced variations in solute and water transport in rat nephrons in rat nephrons in vivo and rabbit nephron segments perfused in vitro. The data obtained in these studies will be interpreted within the framework of quantitative models designed to yield values of the membrane transport parameters which most clearly characterize the process under consideration. Such information is essential for an understanding of the normal mechanisms controlling solute and volume homeostasis, as well as for an understanding of the mechanisms which underlie alterations in these homeostatic processes which are frequently encountered in clinical medicine.